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1.
Appl Microbiol Biotechnol ; 77(2): 457-67, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17846760

RESUMO

The formation and activity of an As(III)-oxidising biofilm in a bioreactor, using pozzolana as bacterial growth support, was studied for the purpose of optimising fixed-bed bioreactors for bioremediation. After 60 days of continuous functioning with an As(III)-contaminated effluent, the active biofilm was found to be located mainly near the inflow rather than homogeneously distributed. Biofilm development by the CAsO1 bacterial consortium and by Thiomonas arsenivorans was then studied both on polystyrene microplates and on pozzolana. Extra-cellular polymeric substances (EPS) and yeast extract were found to enhance bacteria attachment, and yeast extract also appears to increase the kinetics of biofilm formation. Analysis of proteins, sugars, lipids and uronic acids indicate that sugars were the main EPS components. The specific As(III)-oxidase activity of T. arsenivorans was higher (by ninefold) for planktonic cells than for sessile ones and was induced by As(III). All the results suggest that the biofilm structure is a physical barrier decreasing As(III) access to sessile cells and thus to As(III)-oxidase activity induction. The efficiency of fixed-bed reactors for the bioremediation of arsenic-contaminated waters can be thus optimised by controlling different factors such as temperature and EPS addition and/or synthesis to increase biofilm density and activity.


Assuntos
Arsênio/metabolismo , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Betaproteobacteria/crescimento & desenvolvimento , Biofilmes/crescimento & desenvolvimento , Bactérias/genética , Bactérias/isolamento & purificação , Betaproteobacteria/metabolismo , Biodegradação Ambiental , Reatores Biológicos , Meios de Cultura , Sedimentos Geológicos/microbiologia , Ouro , Microbiologia Industrial/métodos , Microscopia Eletrônica de Varredura , Mineração , Oxirredução
2.
Ann Hematol ; 83(7): 414-9, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15085385

RESUMO

The purpose of this study was to investigate the prognostic effects of four biological markers, BCL2, TP53, Ki-67, and P-glycoprotein, and their possible clinical relevance in addition to the international prognostic index (IPI) in diffuse large B-cell lymphoma (DLBCL). A total of 405 patients with aggressive lymphoma, stage II-IV, between 18 and 67 years, were randomized in a trial comparing CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Of these, 267 cases were classified as DLBCL, with adequate paraffin blocks available in 207 cases, enabling immunohistochemical assessment of the expression of BCL2, TP53, P-glycoprotein, and Ki-67. In a multivariate analysis, stratified for IPI, high BCL2 expression (>10%) low (<60%) expression of Ki-67, and high TP53 protein expression (>75%) were shown to provide additional prognostic information with regard to overall or failure-free survival. We found no association between expression of P-glycoprotein and outcome. Assessment of BCL2 positivity might be introduced as part of the routine investigation in patients with DLBCL, but further studies are necessary to confirm the clinical relevance of Ki-67 and TP53 expression.


Assuntos
Linfoma Difuso de Grandes Células B/mortalidade , Proteínas de Neoplasias/análise , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Bleomicina/administração & dosagem , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Antígeno Ki-67/análise , Leucovorina/administração & dosagem , Tábuas de Vida , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/química , Noruega/epidemiologia , Prednisona/administração & dosagem , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/análise , Fatores de Risco , Análise de Sobrevida , Suécia/epidemiologia , Resultado do Tratamento , Proteína Supressora de Tumor p53/análise , Vincristina/administração & dosagem
3.
J Appl Microbiol ; 93(4): 656-67, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12234349

RESUMO

AIMS: To select an autotrophic arsenic(III)-oxidizing population, named CASO1, and to evaluate the performance of the selected bacteria in reactors. METHODS AND RESULTS: An As(III)-containing medium without organic substrate was used to select CASO1 from a mining environment. As(III) oxidation was studied under batch and continuous conditions. The main organisms present in CASO1 were identified with molecular biology tools. CASO1 exhibited significant As(III)-oxidizing activity between pH 3 and 8. The optimum temperature was 25 degrees C. As(III) oxidation was still observed in the presence of 1000 mg l(-1) As(III). In continuous culture mode, the As(III) oxidation rate reached 160 mg l(-1) h(-1). The CASO1 consortium contains at least two organisms - strain b3, which is phylogenetically close to Ralstonia picketii, and strain b6, which is related to the genus Thiomonas. The divergence in 16S rDNA sequences between b6 and the closest related organism was 5.9%, suggesting that b6 may be a new species. CONCLUSIONS: High As(III)-oxidizing activity can be obtained without organic nutrient supply, using a bacterial population from a mining environment. SIGNIFICANCE AND IMPACT OF THE STUDY: The biological oxidation of arsenite by the CASO1 population is of particular interest for decontamination of arsenic-contaminated waste or groundwater.


Assuntos
Arsênio/metabolismo , Betaproteobacteria/classificação , Betaproteobacteria/crescimento & desenvolvimento , Reatores Biológicos , Ecossistema , Betaproteobacteria/isolamento & purificação , Betaproteobacteria/metabolismo , Meios de Cultura , DNA Ribossômico/análise , Ouro , Microbiologia Industrial/métodos , Mineração , Dados de Sequência Molecular , Oxirredução , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do Solo
4.
Acta Oncol ; 40(4): 505-11, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11504311

RESUMO

The aim of this study was to investigate whether there is an association between overexpression of cyclin D1 and response to therapy. Immunohistochemical overexpression of cyclin D1 was determined in paraffin-embedded specimens from diagnostic biopsies of 89 primary cases of squamous cell carcinoma of the head and neck (SCCHN), using a polyclonal antiserum. The tumor response rates were estimated after curative treatment (i.e. surgery and/or radiotherapy and/or chemotherapy). Patients whose tumors were overexpressing cyclin D1 showed complete or partial response to neoadjuvant chemotherapy with cisplatin/5-FU. In addition, a majority of cyclin D1 negative tumors did not respond at all to this treatment (p = 0.02, Fisher's exact test). This study indicates that immunohistochemical assessment of cyclin D1 expression in SCCHN could be a new predictive marker to select a subgroup of patients that will benefit from neoadjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/biossíntese , Carcinoma de Células Escamosas/tratamento farmacológico , Quimioterapia Adjuvante , Ciclina D1/biossíntese , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Terapia Neoadjuvante , Proteínas de Neoplasias/biossíntese , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Radioisótopos de Cobalto/uso terapêutico , Terapia Combinada , Ciclina D1/genética , Fluoruracila/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Tábuas de Vida , Proteínas de Neoplasias/genética , Aceleradores de Partículas , Teleterapia por Radioisótopo , Radioterapia Adjuvante , Radioterapia de Alta Energia , Indução de Remissão , Análise de Sobrevida
5.
Scand J Infect Dis ; 33(1): 27-32, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11234974

RESUMO

The presence of HIV in the placenta was analysed in relation to virological and immunological factors and vertical transmission of HIV in 39 pregnancies between 1989 and 1993 among 37 HIV-1-infected women without zidovudine prophylaxis. HIV-1 was detected in 12 of 37 (31%) placentas by immunohistochemistry and in 3 of 18 by PCR. Altogether 14/39 (36%) placentas bore evidence of HIV-1 infection, although there was no relation with the outcome of HIV infection in the child. Neither was there a relation between placental infection and either CD4 cell counts or HIV-1 RNA levels. However, HIV-1 was isolated from plasma in 20 of 39 (50%) pregnancies, which was inversely related to the presence of HIV in the placenta. When HIV-1 was identified in the placenta, HIV-1 was isolated from plasma in 3/14 (21%) pregnancies, vs 17/25 (68%) when it was not (p = 0.01), with a relative risk of having a placenta positive for HIV of 3.9 in pregnancies with a negative plasma HIV isolation. This inverse relation may point to differences in tropism between HIV-1 in placenta and plasma. The results show that the placental barrier prevents HIV transmission, irrespective of whether HIV enters the placenta or not.


Assuntos
Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Transmissão Vertical de Doenças Infecciosas , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/imunologia , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Estudos Prospectivos , Carga Viral
6.
Genes Chromosomes Cancer ; 30(2): 161-7, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11135432

RESUMO

Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 salivary gland tumors that had been investigated by banding analysis. Five cases were pleomorphic adenoma (PA), three were adenoid cystic carcinoma, and one case each was mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma (CaPA), and adenocarcinoma. All 11 cases were selected on the basis that they had shown rearrangement of 6q or 9p or had unresolved aberrations after karyotyping. The COBRA-FISH and FISH analyses led to a revised karyotype in all informative cases and made it possible to clarify almost all chromosomal rearrangements occurring in the tumors. Of particular note were the confirmation of the existence of 6q deletions, a common change in salivary gland carcinomas, and the demonstration that a seemingly balanced t(6;9) resulted in del(6q). Other rearrangements that were revealed by FISH included amplification of 12q sequences (MDM2 and CDK4) in one PA. We also investigated the status of the PLAG1 gene in four cases (one PA, one CaPA, one adenoid cystic carcinoma, and one mucoepidermoid carcinoma) with 8q12 rearrangements. Only in the former two cases were the FISH results compatible with intragenic rearrangements. Overall, the results of the study show that, even with good banding quality and in karyotypes of modest complexity, much new information will be gained by supplementing the banding analysis with a multicolor FISH approach, such as COBRA-FISH.


Assuntos
Aberrações Cromossômicas/genética , Hibridização in Situ Fluorescente/métodos , Neoplasias das Glândulas Salivares/genética , Adulto , Idoso , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 9/genética , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Translocação Genética/genética
7.
Br J Cancer ; 83(6): 775-81, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10952783

RESUMO

Vascular endothelial growth factor (VEGF) has been identified as the substance that increases the permeability and proliferation of vascular endothelial cells. We examined the clinical significance of VEGF expression in 60 head and neck squamous cell carcinomas using the methods of Western blot, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR), comparatively, and analysed the relationship between VEGF status in Western blot and tumour size, lymph-node status, histologic grade and disease-free survival (DFS) rate. Western blot analysis revealed high VEGF expressors (tumour/normal tissue density >/= 3-fold) in 26 patients (43%) and low VEGF expressors (< 3-fold) in 34 patients (57%). The results of the Western blot analysis correlated significantly with those of the RT-PCR (P = 0.00007) or immunohistochemistry (P = 0. 00006). High VEGF expressors are associated with the progression of lymph-node spread (P = 0.0009), which are correlated with poor DFS. The 2-year DFS rate of high VEGF expressors (30%) was significantly lower than that of low VEGF expressors (78%) (P = 0.0008). Multivariate analysis showed VEGF expression and stage were independent predictors for the DFS (P = 0.045 and 0.041, respectively). VEGF expression may play an important role in progression of HNSCC.


Assuntos
Carcinoma de Células Escamosas/química , Fatores de Crescimento Endotelial/biossíntese , Neoplasias de Cabeça e Pescoço/química , Linfocinas/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Intervalo Livre de Doença , Fatores de Crescimento Endotelial/análise , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Linfocinas/análise , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
8.
Oral Oncol ; 36(2): 194-8, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10745172

RESUMO

Tongue squamous cell carcinoma makes up a large percentage of head and neck cancers, and the incidence among young patients is increasing. The aim of this study was to reveal the correlation between cyclin D1 (CCND1) expression and clinical and histologic features. We performed an immunohistochemical study on the level of CCND1 expression in tumor specimens obtained from 94 patients with tongue squamous cell carcinoma. The relationship between the expression and the following features such as age, sex, smoking and alcohol intake history, T, N, histologic grade, and multiple primary cancer was analyzed. Eighteen patients (19%) showed CCND1 overexpression (tumor cell nuclei positivity >/=50%). The 5-year survival rate of high CCND1 expressors was 39%, which was significantly poor (p=0.04). N classification correlated with CCND1 expression. CCND1 overexpression is associated with poor survival associated with progression of lymph node spread in patients with tongue squamous cell carcinomas. CCND1 expression may be a useful biologic marker for prognosis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Ciclina D1/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias da Língua/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Imuno-Histoquímica , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Fumar/efeitos adversos , Análise de Sobrevida , Neoplasias da Língua/patologia
9.
Genes Chromosomes Cancer ; 28(1): 66-76, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10738304

RESUMO

Cytogenetic analysis of short-term cultures from 105 squamous cell carcinomas of the larynx (LSCC) revealed clonal chromosome aberrations in 56 tumors. Simple karyotypic changes (less than four aberrations per clone) were found in 24 cases, and the remaining 32 tumors had complex karyotypes with multiple numerical as well as unbalanced structural rearrangements. Extensive intratumor heterogeneity, in the form of multiple related subclones or unrelated clones, was observed in a large fraction of the tumors. The structural changes most often affected chromosomes 3, 1, 11, 7, 2, 15, 5, 4, 8, and 12, with rearrangements in the centromeric regions, i.e., the centromeric bands p10 and q10 and the juxtacentromeric bands p11 and q11, accounting for 43% of the total breakpoints. The most common imbalances brought about by numerical and unbalanced structural rearrangements were loss of chromosomal region 3p21-pter, chromosome arms 4p, 6q, 8p, 10p, 13p, 14p, 15p, and 17p, and gain of chromosomal regions 3q21-qter, 7q31-pter, and 8q. Among 17 recurrent aberrations identified, the most common were i(8q), hsr(11)(q13), i(3q), i(5p), and del(3)(p11). No statistically significant association was found between major karyotypic features and histological differentiation or TNM stage. The karyotypic features of the LSCC were also compared with previously published oral SCC, a subgroup of SCC that has been more extensively characterized cytogenetically. No clear-cut karyotypic differences were found between LSCC and oral SCC, with the exception that i(8q) was significantly more frequent among the latter.


Assuntos
Carcinoma de Células Escamosas/genética , Aberrações Cromossômicas/genética , Neoplasias Laríngeas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Aberrações Cromossômicas/epidemiologia , Aberrações Cromossômicas/patologia , Transtornos Cromossômicos , Células Clonais , Feminino , Humanos , Cariotipagem , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade
10.
Int J Cancer ; 85(6): 811-4, 2000 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-10709101

RESUMO

The nature and pathogenesis of inverted papilloma of the nose and paranasal sinuses are debated. Evidence suggesting a viral association is controversial, and epidemiological evidence has pointed to tobacco smoking as a potential etiologic factor. A retrospective regional cohort of 197 patients with sinonasal papilloma was compared with a cohort of 1583 patients with nasal polyps showing a similar distribution by age and sex. All instances of head-and-neck carcinoma diagnosed in both cohorts during a 38-year calendar period were culled from the regional cancer registry, the incidence rate ratio was computed (papilloma:polyp, on tumors detected at the time of or prior to the index diagnosis), and the clinical details were obtained. Nine instances of oral or laryngeal squamous-cell carcinoma, all in men, were identified in the papilloma cohort, and 7 labial, oral or laryngeal carcinomas (2 in women) in patients with polyps. In addition, 5% of the papillomas progressed to sinonasal carcinoma, including 2 cases among those with other primary head-and-neck carcinomas. The incidence-rate ratio for non-sinonasal head-and-neck carcinoma was 12.8 (95% CI, 3. 7 to 50; p < 0.0001). Among the papilloma patients with oral/laryngeal carcinoma, 8 smoked tobacco. Inverted sinonasal papilloma is associated with an increase in non-sinonasal head-and-neck carcinoma, and tobacco may be a causative link.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Papiloma Invertido/epidemiologia , Neoplasias dos Seios Paranasais/epidemiologia , Idoso , Transformação Celular Neoplásica , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fumar
11.
Acta Radiol ; 41(1): 22-6, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10665865

RESUMO

PURPOSE: To describe and report the neuroradiological findings and clinical features in a patient with familial haemophagocytic lymphohistocytosis (FHL), a rare hereditary immune dysregulation in early childhood characterised by multisystem involvement, including in approximately 30% of cases also the central nervous system (CNS). MATERIAL AND METHODS: Serial brain MR examinations were carried out in a 4.5-year-old boy with FHL, finally complicated with Epstein-Barr virus (EBV)-driven posttransplantation lymphoma. RESULTS: Multiple brain MR examinations before and after contrast enhancement showed discrete perivascular non-enhancing areas of high signal intensity on T2 images, and later also an enhancing lesion in the right caudate nucleus. CONCLUSION: FHL should be included in the differential diagnosis of patchy white matter abnormalities in young patients. EBV-driven post-transplantation lymphoma, which may present as meningial and/or parenchymal CNS infiltration, is a differential diagnostic problem.


Assuntos
Encéfalo/patologia , Histiocitose de Células não Langerhans/diagnóstico , Imageamento por Ressonância Magnética , Pré-Escolar , Diagnóstico Diferencial , Histiocitose de Células não Langerhans/genética , Humanos , Lactente , Recém-Nascido , Masculino
12.
Ann Oncol ; 10(9): 1079-86, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10572606

RESUMO

BACKGROUND: The long-term survival of patients with advanced stage aggressive lymphoma has not improved significantly during the last twenty years. In a randomised trial, the efficacy of MACOP-B, a six-drug weekly chemotherapy regimen, was compared to CHOP, the current standard regimen, in terms of overall and failure-free survival, toxicity and health related quality of life. PATIENTS AND METHODS: Four hundred five patients with aggressive lymphoma, stage II-IV, age 18-67, were randomised to receive either 12 weeks of MACOP-B or 8 courses of CHOP over 24 weeks. Special emphasis was put in the definition of Ann Arbor stage in extranodal disease. A subset of 95 patients also entered a quality of life study, based on the EORTC QLQ-C30. RESULTS: Thirty-one patients were ineligible. Among the remaining 374 patients, the median age was 52 years. According to the age-adjusted International Prognostic Index, 37% were 'high-intermediate' or 'high-risk' patients. No difference could be demonstrated, either in overall survival (60% at five years in the MACOP-B group and 59% in the CHOP group) or in failure-free survival (47% at five years with MACOP-B and 44% with CHOP). In terms of quality of life, physical function and global quality of life were more impaired in patients receiving MACOP-B, who also exhibited more non-haematological toxicity. CONCLUSION: No superiority of MACOP-B compared to CHOP could be demonstrated. CHOP remains the treatment of choice in low-risk patients. At present, intensified or experimental treatment should be reserved for high-risk disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Análise Multivariada , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prognóstico , Qualidade de Vida , Taxa de Sobrevida , Fatores de Tempo , Falha de Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos
13.
Am J Clin Pathol ; 112(1 Suppl 1): S40-52, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10396300

RESUMO

The cell cycle consists of an initial growth phase (G1), DNA replication (S), a gap phase (G2), and mitosis (M), after which the cell may differentiate or enter the resting state (G0). The cycle is driven by a number of positive and negative regulatory phosphorylation and dephosphorylation events, involving protein kinases, protein phosphatases, cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors, that ultimately impinge on the activity of transcription factors. Unreplicated or damaged DNA blocks the progression of the cell cycle at checkpoints, including a late G1 checkpoint regulated by the dephosphorylated retinoblastoma protein and a late G2 checkpoint regulated by the phosphorylation of cyclin-dependent kinase 1 complexed with cyclin B. Many cell cycle regulator genes may be considered proto-oncogenes or tumor suppressor genes, and point mutations, amplifications, deletions, or rearrangements involving their loci, particularly those in the "RB pathway," are associated with various tumors. A number of molecular techniques may be used to detect genomic alterations or posttranscriptional modifications, but immunohistochemistry remains the most common method to determine expression levels of a regulatory protein. Multivariate analysis of the usefulness in prognosis has been applied most often for the general proliferation antigen Ki-67.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Neoplasias/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/genética , Análise Custo-Benefício , DNA de Neoplasias/análise , Técnicas Genéticas/economia , Humanos , Neoplasias/patologia
14.
J Pathol ; 187(5): 582-7, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10398125

RESUMO

Skin biopsy sections of Kaposi's sarcoma (KS) from 25 patients (5 AIDS-related, 20 classical cases) were histologically staged and hybridized in situ with oligonucleotide probes for constitutively transcribed human herpesvirus 8 (HHV-8) mRNA T0.7 and T1.1 using a colourimetric technique. T1.1 increases during experimental induction of the viral lytic phase in the HHV-8-infected lymphocytes of primary effusion lymphoma and its colourimetric detection in KS cells presumably corresponds to virion production. Immunostaining with anti-CD20, CD45RO, MAC 387, and alpha-smooth muscle actin was performed following T1.1 in situ hybridization (ISH). When the amount of T0.7 was above the detection threshold, the signal was made up of multiple coarse intranuclear dots in most spindle cells. Of the six early-stage lesions, none produced a T1.1 hybridization signal. Two of four AIDS-related and two of eight classical lesions with incipient spindle cell growth produced rare but distinct dense intranuclear T1.1 signals in endothelial cells lining narrow tubes. In contrast, eight of ten (all classical KS) mature spindle cell lesions displayed a signal, scattered in up to 2 per cent of spindled endothelial cells. Cell types other than endothelium produced no T1.1 hybridization signal in double stains. The results are consistent with other published data indicating latent HHV-8 infection in endothelium and its tumour cell progeny, with simultaneous virion production in a small subset of cells. Immunodeficiency may not influence the number of cells lytically infected with HHV-8 in early KS, in contradistinction to other herpesviruses with latent-lytic cycles.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Herpesvirus Humano 8/isolamento & purificação , RNA Viral/análise , Sarcoma de Kaposi/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Herpesvirus Humano 8/fisiologia , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Latência Viral
15.
J Cell Sci ; 112 ( Pt 12): 1855-64, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10341205

RESUMO

The local growth of tumors and their ability to metastasize are crucially dependent on their interactions with the surrounding extracellular matrix. Tenascin-C (TNC) is an extracellular matrix protein which is highly expressed during development, tissue repair and cancer. Despite the high levels of TNC in the stroma of primary and metastatic tumors, the function of TNC is not known. In the present study we have crossed TNC-null mice with a mouse strain where both female and male mice spontaneously develop mammary tumors followed by metastatic disease in the lungs. We report that the absence of TNC had no effect on the temporal occurrence of mammary tumors and their metastatic dissemination in lungs. Furthermore, the number and size of tumors, the number and size of metastatic foci in the lungs, the proliferation rate and apoptosis of tumor cells and tumor angiogenesis were not altered in the absence of TNC. Histological examination revealed that the tumor organisation, however, was modulated by TNC. In the presence of TNC both primary as well as metastatic tumors were organised in large tumor cell nests surrounded by thick layers of extracellular matrix proteins. In the absence of TNC these tumor cell nests were smaller but still separated from each other by extracellular matrix proteins. In addition, the TNC-null stromal compartment contained significantly more monocytes/macrophages than tumor stroma from TNC wild-type mice. Using in vitro coculture experiments we show that TNC-null tumor cells were still able to activate the TNC gene in fibroblasts which express low basal levels of TNC. Altogether these data indicate that TNC has a very limited role during the spontaneous development and growth of mamary tumors and their metastasis to the lungs.


Assuntos
Macrófagos/fisiologia , Neoplasias Mamárias Experimentais/fisiopatologia , Monócitos/fisiologia , Tenascina/fisiologia , Animais , Divisão Celular/fisiologia , Técnicas de Cocultura , Feminino , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/secundário , Macrófagos/patologia , Masculino , Neoplasias Mamárias Experimentais/etiologia , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Transgênicos , Monócitos/patologia , Células Estromais/patologia , Células Estromais/fisiologia
16.
Cancer ; 85(5): 1011-7, 1999 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10091782

RESUMO

BACKGROUND: p27, a cyclin-dependent kinase inhibitor, regulates progression from G1 to S phase. There have been a few clinical reports of low p27 expression associated with poor survival among patients with cancer; however, there have been no reports of such an association in cases of head and neck cancer. The authors investigated whether p27 expression in patients with oral tongue squamous cell carcinoma was associated with their prognosis. METHODS: Ninety-four patients with oral tongue squamous cell carcinoma were analyzed. The authors performed p27 immunohistochemistry on all patients and Western blot analysis on 19 available patients. Cox proportional hazards regression analysis that included gender, history of smoking and alcohol usage, presence of multiple primary cancers, stage, histologic grade, and p27 status was used to identify the multivariate predictive value of prognostic factors. RESULTS: Twenty-six patients had high p27 expression (> or =50% tumor cell nuclei positive), and 68 patients had low p27 expression (<50%) by immunohistochemistry. In those with low p27 expression, N(+) and advanced T (T3 or T4) were significantly higher than in those with high p27 expression (P = 0.02 and 0.04). The 5-year survival rate in the low p27 group was 44%, whereas that in the high p27 group was 68%, indicating a significant difference (P = 0.04). p27 expression was inferred from Western blot analysis, and an arbitrary quantity (<1, 1-5, or > or =5) from the ratio of tumor to normal tissue density was used to characterize, resulting in 8 (42%), 3 (16%), and 8 (42%) patients in the low (<1-fold), intermediate (1-5-fold), and high (> or =5-fold) groups, respectively. Results of immunohistochemical analysis for p27 were significantly correlated with those of Western blot analysis (P = 0.02). Multivariate analysis revealed that low intensity of p27 expression and advanced stage (Stage III or IV) were predictors of reduced survival (P = 0.02 and 0.001). CONCLUSIONS: Low p27 expression was associated with increasing lymph node metastasis and stage of tumor and resulted in a poor prognosis for patients with oral tongue squamous cell carcinoma. p27 is apparently a significant predictor of survival.


Assuntos
Carcinoma de Células Escamosas/química , Regulação Neoplásica da Expressão Gênica , Proteínas dos Microfilamentos/análise , Proteínas Musculares , Neoplasias da Língua/química , Actinas/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Risco , Fatores de Risco , Análise de Sobrevida
17.
Br J Cancer ; 78(8): 1084-90, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9792155

RESUMO

Survival in squamous cell carcinoma of the head and neck (HNSCC) was compared with overexpression and mutation of the p53 gene. Archival tissue from 77 tumours was analysed for protein expression using immunohistochemistry (IHC) with the monoclonal antibody Do-7, and for the presence of mutation in exons 5-8 using single-stranded conformation polymorphism (SSCP), followed by DNA sequencing in SSCP-positive cases. p53 expression was scored as high (>70% nuclei stained) in 25 (32%) tumours, as intermediate (10-70% nuclei stained) in 19 (25%) tumours and as low (<10% nuclei stained) in 33 (43%) tumours. Twelve (18%) tumours exhibited gene mutation (ten missense and two nonsense mutations) and an additional five tumours contained changes that could not result in amino acid substitution or protein truncation. There was no correlation between gene expression and mutation, mutations being equally frequent in tumours with either high (4/25), intermediate (4/19) or low protein expression (4/33). Fifty-eight patients were eligible for survival analysis. There was a strong correlation between p53 mutation and cause-specific survival; median survival among mutated cases was 12.5 months compared with >160 months among non-mutated patients (P < 0.005). There was no correlation between p53 overexpression and survival. The results suggest that p53 mutation status is an important prognostic factor in HNSCC, and that IHC analysis of protein overexpression is an inadequate measure of gene mutation in these tumours.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Genes p53 , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Mutação , Proteína Supressora de Tumor p53/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples
18.
Br J Cancer ; 78(3): 292-5, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9703273

RESUMO

The paradigm that human malignancies are monoclonal has been questioned during recent years by the finding of unrelated, cytogenetically aberrant clones in short-term cultures from certain tumour types, notably carcinomas of the breast, skin and upper aerodigestive tract. In order to analyse whether cytogenetically unrelated clones are also unrelated at the molecular level, we analysed the X-chromosome inactivation status in cell cultures from a cytogenetically highly polyclonal acinic cell carcinoma of the parotid gland. By using cell cultures dominated by a single abnormal clone, obtained through in vitro culturing for 3-5 passages, we showed that the different clones must indeed have originated from different cells.


Assuntos
Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/patologia , Neoplasias Parotídeas/genética , Neoplasias Parotídeas/patologia , Idoso , Aberrações Cromossômicas , Células Clonais , Mecanismo Genético de Compensação de Dose , Feminino , Humanos , Cariotipagem
19.
Cancer Lett ; 126(1): 59-65, 1998 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-9563649

RESUMO

Of 39 males diagnosed with sinonasal adenocarcinomas over 30 years in the Lund University Hospital catchment area (1.5 million inhabitants), archival tumor tissue was available from 29. Of these, 16 had been exposed to wood dust and three had been exposed to leather dust. The intestinal-type and papillary adenocarcinomas were more common in the exposed patients (P = 0.0002, Fisher's exact test). The tumors from all but one of the 29 sinonasal adenocarcinomas could be analyzed for point mutations at codons 12, 13 and 61 of the K-ras gene. Four mutations were detected in the 28 tumors. The three mutations in the patients exposed to wood and leather dust were all G:C --> A:T transitions, with two at position 2 of codon 12 and one at position 2 of codon 13. The high proportion of G:C --> A:T mutations in this rare tumor may reflect a genotoxic agent in wood and leather dust.


Assuntos
Adenocarcinoma/induzido quimicamente , Adenocarcinoma/genética , Genes ras , Doenças Profissionais/induzido quimicamente , Neoplasias dos Seios Paranasais/induzido quimicamente , Neoplasias dos Seios Paranasais/genética , Mutação Puntual , Curtume , Madeira , Humanos , Masculino , Doenças Profissionais/genética
20.
Cancer Genet Cytogenet ; 100(1): 52-6, 1998 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-9406581

RESUMO

Angiosarcomas are rare malignant vascular tumors, most commonly found in the skin or superficial soft tissue. We found clonal chromosome aberrations in four short-term cultured angiosarcomas. Two cases were diagnosed as epithelioid angiosarcomas, and one as postmastectomy angiosarcoma. Two of the tumors were deep-seated and two were superficial. Angiosarcomas from deep, soft tissue are extremely rare and have never been cytogenetically investigated before. The chromosome number ranged from hypodiploid to hypertriploid. When the results from the present study were combined with data on the four previously reported cytogenetically aberrant angiosarcomas, the most frequently rearranged chromosomes were 5, 7, 8, 13, 15, 20, 22, and the Y chromosome. Recurrent changes, each found in three of these eight angiosarcomas, were gains of 5pter-p11, 8p12-qter, and 20pter-q12, losses of 7pter-p15 and 22q13-qter, and -Y in two of three men.


Assuntos
Aberrações Cromossômicas , Hemangiossarcoma/genética , Neoplasias de Tecidos Moles/genética , Adulto , Idoso , Feminino , Humanos , Masculino
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